Collection and analysis of a volume of exhaled gas with compensation for the frequency of a breathing parameter

ABSTRACT

Apparatuses are described to accurately determine a gas concentration of a sample of a patient&#39;s breath. The apparatuses may include a sample compartment, a breath speed analyzer, a gas analyzer, and a processor. The sample compartment includes an inlet that receives the breath. The breath speed analyzer determines the speed of a portion of the breath. The gas analyzer determines a gas concentration. The processor includes an algorithm that determines a degree of non-homogeneity of the sample based on the speed, and a corrected gas concentration based on the degree of non-homogeneity. In some variations, the gas correction is determined independently of patient cooperation. Apparatuses may be tuned based on the intended population&#39;s expected breathing pattern ranges such that the sample compartment is filled with a homogenous end-tidal gas sample regardless of an individual&#39;s breathing pattern. These apparatuses are useful, for example, for end-tidal CO analysis. Methods are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/578,811, filed Dec. 21, 2011, the disclosure of which is incorporatedherein in its entirety.

FIELD OF THE INVENTION

Described here are devices and methods for the analysis of breathexhalant for diagnostic purposes. More specifically, devices and methodsfor sampling and analysis of gas from a person's breath for correlationto and diagnosis of an underlying physiologic condition are described.

BACKGROUND

There are two general techniques employed for obtaining a person'sbreath for gas analysis. In a first technique a person can cooperativelybreathe into an instrument, which receives the gas for analysis. In asecond technique an instrument can obtain a gas sample from the person'sairway independent of the person's cooperation. In either technique,achieving a precise collection and precise analysis of a gas from aspecific portion of the breathing cycle can be challenging, given theoften random and erratic nature of a breathing pattern. For example,reliably measuring breath CO at exactly the end-tidal portion ofexhalation, with high levels of accuracy and precision (for example <0.5ppm accuracy), has proven difficult. Typically, a measurement of breathCO₂ is used to determine the end-tidal portion of the breath, and gasfrom that portion of the breath can be sampled and analyzed accordingly.Using an end-tidal CO₂ signal is a convenient approach in that thetechnology is well known, and provides an instantaneous measurement ofthe breath waveform. However, in order to obtain accuracy and precisionin the remainder of the overall system, the instrumentation considersonly some of the possible external factors that may be useful.

Typically, a constant flow rate is employed for withdrawing the gas fromthe person, for a fixed collection time, and placing the drawn sample ina fixed volume sample compartment. When using this approach, there maybe breath pattern related inaccuracies. For example, some of the samplecompartment may have non-end-tidal gas in it, or only a fraction of theend-tidal portion of the breath might get sampled and stored in thesample compartment for analysis. While the repeatability at a certainbreath rate is very good, the accuracy may vary as the breath ratevaries, because of the pneumatics and timing of the system.

Therefore, it may be beneficial to improve on the accuracy of knownsystems in a way that is equally accurate across a range of breathpatterns and breath rates. To this end, various approaches andalgorithms have been conceived and described herein.

BRIEF SUMMARY

Described herein are breath gas analyzers that achieve an accuratecompositional analysis of a breath-borne gas from a specific portion ofa breath. The system can accommodate a wide range of breathing patternsand rates without losing accuracy. The system can assure that enoughvolume of gas is obtained for the analysis to be sufficiently accurate,and that the gas obtained is from the desired portion of the breath, andis representative of the entire desired portion of the breath. In somevariations, these advantages are achieved by modulating the gas samplingflow rate depending on the breath pattern, and/or by obtaining gassamples from the desired portion of the breath for multiple breathsuntil a threshold volume of gas is obtained for analysis, and/or byapplying a correction factor to the computed result to compensate forheterogeneity of the sampled gas. In addition to these methods forobtaining target volumes of gas, some variations may identify thedesired portion of the breath in order to accurately sample the correctportion of the breath and/or tune the system to always collect foranalysis a substantially homogenously end-tidal sample regardless ofbreathing pattern.

To achieve the above features, variations of a breath analyzer or methodfor analyzing breath may include one or more of the following benefits:identification of different sub-portions of an expiratory phase;accurate sample collection from a desired sub-portion of the expiratoryphase; assured collection of a predetermined quantity of gas foranalysis by a gas composition analyzer; reliability and repeatable for awide variety of breathing patterns that are expected to be encountered.

In one variation, a method for breath analysis comprises measuring atime-related parameter of a person's breathing pattern, collecting gasfrom a target portion of at least one of the person's breaths into asample compartment having a target volume, adjusting the gas collectionbased on the time-based-parameter, and analyzing the collected gas todetermine a compositional parameter of the gas. In further variations,adjusting the gas collection can include at least one selected from thegroup consisting of: (1) adjusting the gas collection speed, (2)adjusting the number of breaths the gas is collected from, and (3)adjusting for the homogeneity of the collected gas with a correctionfactor. In yet further variations, the time-based-parameter comprises atleast one parameter selected from the group consisting of: (1) breathrate, (2) end-tidal time period, (3) expiratory time period, (4)inspiratory time period, (5) breath period. In further variations, thetarget portion of the breath comprises the end-tidal portion and thecompositional parameter comprises carbon monoxide. In furthervariations, the target portion of the breath comprises at least onephase selected from the group consisting of: (1) an expiratory phase;(2) an end-tidal phase; (3) a beginning portion of exhalation; (4) amiddle portion of exhalation; (5) a last portion of exhalation; (6) apost-expiratory period; and (7) an inspiratory pause. In furthervariations, measuring a time-based parameter comprises at least onetechnique selected from the group consisting of: (1) capnometry, (2)monitoring airway pressure, (3) monitoring airway temperature, (4)monitoring airway flow, (5) plethysmography, (6) monitoring sound, and(7) monitoring exhaled oxygen. In yet further variations, thetime-based-parameter is differentiated to determine a time period of atarget breath portion. Further variations may include defining a starttime and an end time for collecting the gas, wherein defining a starttime and an end time comprises comparing the measured breath parameteragainst at least one selected from the group consisting of: (1) athreshold amplitude of the measured breath parameter; (2) a thresholdtime period of the measured breath parameter, (3) a peak value of themeasured breath parameter, (4) a substantially zero value of themeasured breath parameter, (5) a negative value of the measured breathparameter, (6) a change in slope of the measured breath parameter, and(7) a change in sign of the measured breath parameter. Other variationsmay include defining a start time and an end time for collecting the gaswherein defining a start time and an end time comprises calculating arate of change of the measured breath parameter and comparing it to atleast one selected from the group consisting of: (1) a threshold valueof the rate of change; (2) a zero value of the rate of change; (3) afirst rate of change against a second rate of change; (4) a negativeslope approaching zero; (5) a positive slope approaching zero; (6) apeak positive value of the rate of change; (7) a peak negative value ofthe rate of change; (8) an increasing rate of change; (9) a decreasingrate of change; and (10) a sign change of the rate of change. In furthervariations, collecting the gas further comprises applying a samplingcannula in communication with the sample compartment to the person'sairway, and applying a vacuum to the sampling cannula. Furthervariations may include isolating the sample compartment with an inletvalve, and opening the inlet valve to begin collecting the gas from thetarget breath portion and closing the inlet valve to finish collectingthe gas from the target breath portion. In further variations, the gascollected in the sample compartment comprises at least a portion of abreath from which the time-based breath parameter is measured. Infurther variations, the gas collected in the sample compartmentcomprises at least a portion of a breath that is not a breath from whichthe time-based breath parameter is measured.

In another variation, a method for breath analysis comprises identifyinga time period of a portion of a breath, collecting a gas sample from theportion in a sample compartment having a target volume, wherein the gassample is drawn into the compartment using a flow mechanism, and whereina flow rate of the mechanism is based on the identified time period, andanalyzing the collected gas sample for compositional analysis.

In another variation, a method for breath analysis comprises measuringan end-tidal time period of a person's breathing pattern with a breathsensor, collecting gas from the end-tidal period of at least one of theperson's breaths into a sample compartment having a target volume with aflow mechanism, wherein the collection flow rate of the flow mechanismis adjusted based on the measured end-tidal time period and selected tosubstantially fill the target volume with gas from the end-tidal period,and analyzing the collected gas to determine a compositional parameterof the gas.

In another variation, a method for breath analysis comprises the steps(a) identifying a time period of a portion of a breath, (b) collecting agas sample from the portion in a sample compartment having a targetvolume, wherein the gas sample is drawn into the compartment using aflow mechanism, (c) wherein (a) and (b) are repeated for a number oftimes, wherein the number of times is determined at least in part by theidentified time period, and (d) analyzing the collected gas sample forcompositional analysis.

In another variation, a method for breath analysis comprises (a)measuring an end-tidal time period of a person's breathing pattern witha breath sensor, (b) collecting gas from the end-tidal period of theperson's breath into a sample compartment having a target volume using aflow mechanism, (c) wherein (a) and (b) are repeated until thecompartment is substantially filled with gas from end-tidal periods, and(d) analyzing the collected gas to determine a compositional parameterof the gas. In another variation, the method includes tuning the breathcollection system to always collect a substantially homogenouslyend-tidal sample, regardless of breathing pattern

Also described herein are various breath gas analyzers. In onevariation, an apparatus for analyzing gas in a target portion of aperson's breath cycle comprises a sample compartment of a target volume,a pneumatic system operable to collect gas from a person's breath anddeliver the gas to the sample compartment, a breath sensor operable tomeasure a time-based-parameter of the target portion of the person'sbreath, a control system operable to adjust the pneumatic system basedon the time-based-breath parameter, and an analyzer for analyzing thegas composition. In further variations, a gas flow system adjustment isprovided that comprises at least one adjustment selected from the groupconsisting of: (1) an adjustable speed flow generator; (2) a processorconfigured to execute an algorithm that varies the number of breaths gasis collected from, and (3) a processor configured to execute analgorithm to adjust for the homogeneity of the collected gas with acorrection factor. In further variations, the time-based-componentcomprises at least one component selected from the group consisting of:(1) a breath rate, (2) an end-tidal time period, (3) an expiratory timeperiod, (4) an inspiratory time period, and (5) a breath period. Infurther variations, the target portion of the breath comprises theend-tidal portion and the gas analyzer comprises a carbon monoxideanalyzer. In further variations, the target portion of the breathcomprises at least one portion selected from the group consisting of:(1) an expiratory phase; (2) an end-tidal phase; (3) a beginning portionof exhalation; (4) a middle portion of exhalation; (5) a last portion ofexhalation; (6) a post expiratory phase; and (7) an inspiratory pause.In further variations, the breath sensor comprises at least one selectedfrom the group consisting of: (1) a capnometer, (2) an airway pressuretransducer, (3) an airway temperature sensor, (4) an airway flow sensor,(5) a plethysmograph, (6) a microphone, (7) an oxygen sensor, and (8) anultrasonic sensor. In further variations, the apparatus furthercomprises (1) a differentiator adapted to differentiate the signal fromthe breath sensor and (2) a processor, wherein the processor executes analgorithm to correlate the differentiated signal to the target portionof the breath cycle. In further variations, the apparatus furthercomprises a processor, wherein the processor executes an algorithm todetermine the start time and end time for collecting the gas, whereinthe algorithm comprises a comparison of the measured breath parameteragainst at least one selected from the group consisting of: (1) athreshold value, (2) a threshold time period, (3) a peak value, (4) asubstantially zero value, (5) a negative value, (6) a change in slope,and (7) a change in sign. In further variations, the apparatus comprisesa differentiator to determine a rate-of-change of the measured breathparameter, and a processor to execute an algorithm, wherein thealgorithm comprises a comparison of the rate of change with at least oneselected from the group consisting of: (1) a threshold value; (2) a zerovalue; (3) a first rate of change against a second rate of change; (4) anegative slope approaching zero; (5) a positive slope approaching zero;(6) a peak positive value; (7) a peak negative value; (8) an increasingrate of change; (9) a decreasing rate of change; and (10) a sign changeof the rate of change. In further variations, the apparatus furthercomprises a sampling cannula attachable at a first end to the gasanalysis apparatus and engageable at a second end to the person'sairway; and a flow generator adapted to draw gas from the person'sairway through the sampling cannula to the sample compartment. Infurther variations, the apparatus comprises a valve system arranged toisolate the sample compartment, wherein the control system controls thevalve system to permit gas from the target breath portion to enter thesample compartment. In further variations, the control system is furtheradapted to deliver gas to the sample compartment from the measuredbreath. In further variations, the control system is further adapted todeliver gas to the sample compartment from a breath after the measuredbreath.

In another variation, a breath gas analyzer for analyzing gas in atarget portion of a person's breath comprises a breath sensor foridentifying the target portion of the breath cycle, a processor fordetermining the time period of the target portion, wherein the timeperiod is determined at least in part from the identified portion, a gascollection compartment of a target volume, a pneumatic system fordelivering a gas sample from the target portion of the breath to the gascollection compartment, a control system for adjusting the gas deliveryrate of the pneumatic system based on the determined time period, and agas analyzer for analyzing the composition of the gas.

In another variation, a breath gas analyzer for analyzing gas in theend-tidal portion of a person's breath comprises a breath sensor foridentifying the end-tidal period of the breath cycle, a processor fordetermining the time period of the end-tidal period, wherein the timeperiod is determined at least in part from the identified portion, a gascollection compartment of a target volume, a vacuum source for drawing agas sample from the end-tidal period of the breath to the gas collectioncompartment, a control system for adjusting the flow rate of the vacuumsource based on the determined end-tidal time period to substantiallyfill the compartment with end-tidal gas, and a gas analyzer foranalyzing the composition of the gas.

In another variation, a breath gas analyzer for analyzing gas in atarget portion of a person's breath, comprises a breath sensor foridentifying the target portion of the breath cycle, a processor fordetermining the time period of the target portion, wherein the timeperiod is determined at least in part from the identified portion, a gascollection compartment of a target volume, a pneumatic system fordelivering a gas sample from the target portion of the breath to the gascollection compartment, a control system and algorithm for controllingthe pneumatic system to deliver gas until the compartment issubstantially filled with gas from the target breath portion, and a gasanalyzer for analyzing the composition of the gas.

In another variation, a breath gas analyzer for analyzing gas in atarget portion of a person's breath comprises a breath sensor foridentifying the target portion of the breath cycle, a processor fordetermining the time period of the target portion, wherein the timeperiod is determined at least in part from the identified portion, a gascollection compartment of a target volume, a pneumatic system forcapturing a gas sample from the target portion of the breath into thegas collection compartment, a processor for executing an algorithm forapplying a correction factor to the captured gas sample, wherein thecorrection factor is based on the determined time period of the targetbreath portion to correct for the non-homogeneity of the captured gas,and a gas analyzer for analyzing the composition of the gas.

In another variation, a method for breath analysis comprises (a)identifying a time period of an end-tidal portion of a breath, (b)collecting the end-tidal portion in a sample tube having a samplevolume, wherein a time of collection is based on the identified timeperiod, (c) repeating steps (a) and (b) until the sample volume isfilled with a plurality of end-tidal portions from a respectiveplurality of breaths, and (d) analyzing the collected plurality ofend-tidal portions to determine the concentration of a gas.

In another variation, a breath gas analyzer comprises a system operableto measure at least one characteristic of a patient's breath, aprocessor operable to determine a starting and an ending point of anend-tidal portion of the breath, wherein the determination is based uponthe at least one characteristic, a sample tube comprising a proximalend, a distal end, a first valve coupled to the proximal end, a secondvalve coupled to the distal end, and a sample volume, wherein the samplevolume is configured to store a plurality of end-tidal breath portionsfrom a respective plurality of breaths, and a sensor for analyzing theconcentration of a gas in the stored plurality of end-tidal breaths.

In another variation, a method of collecting an end-tidal portion of apatient's breath comprises identifying a starting point of the end-tidalportion, opening a container configured to collect the end-tidalportion, wherein the container is opened to correlate to the identifiedstarting point of the end-tidal portion, identifying an ending point ofthe end-tidal portion, and closing the container, wherein the containeris closed to correlate to the identified ending point of the end-tidalportion.

In another variation, a gas measurement correction database fordetermining a gas concentration at an inlet of an apparatus is populatedby a method that may include measuring a plurality of gas concentrationsin the apparatus for a respective plurality of known gas concentrationsat the inlet (wherein the gas concentrations are measured at a pluralityof breath rates), deriving a first plurality of polynomial equations(wherein each of the first plurality of polynomial equations fits themeasured gas concentrations of a respective one of the plurality ofbreath rates and wherein each of the first plurality of polynomialequations comprises a coefficient at each order of the equation),deriving a second plurality of polynomial equations (wherein each of thesecond plurality of polynomial equations fits the coefficients of arespective order of the first plurality of polynomial equations whereineach of the second plurality of polynomial equations comprises acoefficient at each order of the equation), and recording each of thecoefficients of the second plurality of polynomial equations in thedatabase. The first plurality of polynomial equations may comprise aplurality of linear equations. The plurality of breath rates may be atleast five in number. The plurality of breath rates may include breathrates of 10 breaths per minute, 20 breaths per minute, 30 breaths perminute, 40 breaths per minute, and 50 breaths per minute. The secondplurality of polynomial equations may comprise a plurality of quadraticequations. The coefficients of the second plurality of polynomialequations may comprise a first plurality of coefficients and a secondplurality of coefficients, wherein the first plurality of coefficientscorrespond to breath rates at or below a predetermined breath rate andthe second plurality of coefficients correspond to breath rates at orabove the predetermined breath rate. The predetermined breath rate maybe 30 bpm. The second plurality of polynomial equations may comprise afirst plurality of quadratic equations and a second plurality ofquadratic equations, wherein each of the first plurality of quadraticequations fits the first plurality of coefficients at each order, andwherein each of the second plurality of quadratic equations fits thesecond plurality of coefficients at each order. The plurality of knowngas concentrations at the inlet may comprise three in number. Theplurality of known gas concentrations at the inlet may comprise at leastone selected from each of the following: a region of relatively lowbreath rate, a region of relatively high breath rate, and a region ofintermediate breath rate.

In another variation, a method for determining a gas concentration of apatient's breath at an inlet of an apparatus may comprises determining abreath rate of the patient, measuring a gas concentration in theapparatus, accessing a database to obtain a first plurality ofcoefficients corresponding to the patient's breath rate, deriving afirst plurality of polynomial equations based on the first plurality ofcoefficients, deriving a second plurality of coefficients by inputtingthe breath rate into each of the first plurality of polynomialequations, deriving a compensation equation using the second pluralityof coefficients, and determining the gas concentration at the inlet byinputting the measured gas concentration into the compensation equation.Each of the first plurality of polynomial equations may be a quadraticequation and the first plurality of coefficients may be three in number.The compensation equation may be linear and the second plurality ofcoefficients may be two in number. The database may include a firstsubset of coefficients and a second subset of coefficients, wherein thefirst subset of coefficients correspond to breath rates at or below apredetermined breath rate and the second subset of coefficientscorrespond to breath rates at or above the predetermined breath rate.The predetermined breath rate may be 30 bpm.

In another variation, an apparatus for analyzing a gas concentration ofa patient's breath may comprise a gas analyzer that measures a gasconcentration in the apparatus, an inlet that receives the patient'sbreath, a breath speed analyzer that determines a breathing parameterfrequency of the patient's breath, a database comprising a plurality ofcoefficients corresponding to a plurality of breathing parameterfrequencies, and a processor containing a non-transitory computerreadable medium containing executable instructions that when executedperform a method of determining the gas concentration of the patient'sbreath at the inlet of the apparatus, wherein the method includesaccessing the database to obtain a first plurality of coefficients basedon the patient's breathing parameter frequency, deriving a firstplurality of polynomial equations based on the first plurality ofcoefficients, deriving a second plurality of coefficients by inputtingthe breathing parameter frequency into each of the first plurality ofpolynomial equations, deriving a compensation equation using the secondplurality of coefficients, and determining the inlet gas concentrationby inputting the measured gas concentration into the compensationequation. The first plurality of polynomial equations may be a quadraticequation and the first plurality of coefficients may be three in number.The compensation equation may be linear and the second plurality ofcoefficients may be two in number. The database may comprise a firstsubset of coefficients and a second subset of coefficients, wherein thefirst subset of coefficients correspond to breathing parameterfrequencies at or below a predetermined breathing parameter frequencyand the second subset of coefficients correspond to breathing parameterfrequencies at or above the predetermined breathing parameter frequency.The predetermined breathing parameter frequency may be 30 bpm.

In another variation, a method for determining a gas concentration of apatient's breath at an inlet of an apparatus includes determining abreathing parameter frequency of the patient, measuring a gasconcentration in the apparatus, accessing a database to obtain aplurality of coefficients based on whether the patient's breathingparameter frequency is at, above, or below a predetermined breathingparameter frequency, wherein the database comprises a first subset ofcoefficients and a second subset of coefficients, wherein the firstsubset of coefficients correspond to breathing parameter frequencies ator below the predetermined breathing parameter frequency and the secondsubset of coefficients correspond to breathing parameter frequencies ator above the predetermined breathing parameter frequency, deriving acompensation equation using the plurality of coefficients, anddetermining the gas concentration at the inlet by inputting the measuredgas concentration into the compensation equation. The predeterminedbreathing parameter frequency may be 30 bpm.

In another variation, an apparatus for analyzing a gas concentration ofa patient's breath may comprise a gas analyzer that measures a gasconcentration in the apparatus, an inlet that receives the patient'sbreath, a breath speed analyzer that determines a breathing parameterfrequency of the patient's breath, a database comprising a plurality ofcoefficients corresponding to a plurality of breathing parameterfrequencies, wherein the database comprises a first subset ofcoefficients and a second subset of coefficients, wherein the firstsubset of coefficients correspond to breathing parameter frequencies ator below a predetermined breathing parameter frequency and the secondsubset of coefficients correspond to breathing parameter frequencies ator above the predetermined breathing parameter frequency, and aprocessor containing a non-transitory computer readable mediumcontaining executable instructions that when executed perform a methodof determining the gas concentration of the patient's breath at theinlet of the apparatus, the method including accessing the database toobtain a plurality of coefficients based on whether the patient'sbreathing parameter frequency is at, above, or below the predeterminedbreathing parameter frequency, deriving a compensation equation based onthe plurality of coefficients, and determining the inlet gasconcentration by inputting the measured gas concentration into thecompensation equation. The predetermined breathing parameter frequencymay be 30 bpm.

In another variation, a method for determining a gas concentration of apatient's breath at an inlet of an apparatus may comprise determining abreathing parameter frequency of the patient, measuring a gasconcentration in the apparatus, accessing a database to obtain aplurality of coefficients corresponding to the patient's breathingparameter frequency, deriving a compensation equation using theplurality of coefficients, and determining the gas concentration at theinlet by inputting the measured gas concentration into the compensationequation. The compensation equation may be a polynomial equation. Thecompensation equation may be linear. The database may comprise a firstsubset of coefficients and a second subset of coefficients, wherein thefirst subset of coefficients correspond to breathing parameterfrequencies at or below a predetermined breathing parameter frequencyand the second subset of coefficients correspond to breathing parameterfrequencies at or above the predetermined breathing parameter frequency.The predetermined breathing parameter frequency may be 30 bpm.

In another variation, an apparatus for analyzing a gas concentration ofa patient's breath comprises a gas analyzer that measures a gasconcentration in the apparatus, an inlet that receives the patient'sbreath, a breath speed analyzer that determines a breathing parameterfrequency of the patient's breath, a database comprising a plurality ofcoefficients corresponding to a plurality of breathing parameterfrequencies, and a processor containing a non-transitory computerreadable medium containing executable instructions that when executedperform a method of determining the gas concentration of the patient'sbreath at the inlet of the apparatus, the method comprising accessingthe database to obtain a plurality of coefficients based on thepatient's breathing parameter frequency, deriving a compensationequation using the plurality of coefficients, and determining the inletgas concentration by inputting the measured gas concentration into thecompensation equation. The compensation equation may be a polynomialequation. The polynomial equation may be a linear equation. The databasemay comprise a first subset of coefficients and a second subset ofcoefficients, wherein the first subset of coefficients correspond tobreathing parameter frequencies at or below a predetermined breathingparameter frequency and the second subset of coefficients correspond tobreathing parameter frequencies at or above the predetermined breathingparameter frequency. The predetermined breathing parameter frequency maybe 30 bpm.

In another variation, an apparatus for collecting gas from a patient'sbreath comprises a sample volume, a flow generator comprising a samplingflow rate (wherein the flow generator may completely, or nearlycompletely, fill the sample volume with an end-tidal portion of thepatient's breath when the patient's breath has a determined breathingparameter frequency), and a processor configured to discard a gascollected from the patient's if a breathing parameter frequency of thepatient exceeds the predetermined breathing parameter frequency. Theflow generator may be a pump. The end-tidal period of the patient'sbreath may be assumed to be a fraction such as one quarter of a breathperiod of the patient, wherein the breath period comprises oneinspiratory and expiratory cycle of the patient's breath.

In another variations, an apparatus for analyzing a gas concentration ofa sample of a patient's breath may comprise a sample compartment with aninlet that receives the patient's breath, a breath speed analyzer thatdetermines the speed of a portion of the patient's breath, a gasanalyzer that determines a gas concentration of the gas in the samplecompartment, and a processor comprising an algorithm that determines acorrected gas concentration based on the speed of a portion of thepatient's breath, wherein the corrected gas concentration is determinedindependently of patient cooperation.

In another variation, an apparatus for analyzing a gas concentration ofa sample of a patient's breath may comprise a sample compartment with aninlet that receives the patient's breath, a breath speed analyzer thatdetermines the speed of a portion of the patient's breath, a gasanalyzer that determines a gas concentration of the gas in the samplecompartment, and a processor comprising an algorithm, wherein thealgorithm determines a degree of non-homogeneity of the breath sample inthe sample compartment based on the speed of a portion of the patient'sbreath, wherein the algorithm determines a corrected gas concentrationbased on the degree of non-homogeneity, and wherein the corrected gasconcentration is determined independently of patient cooperation.

In another variation, an apparatus for analyzing a gas concentration ofa sample of a patient's breath may comprise a breathing parameterfrequency measuring sensor, an algorithm comprising a defined maximumbreathing parameter frequency, a sample compartment with a volume andwith an inlet that receives the patient's breath, a gas analyzer thatdetermines a gas concentration of the gas in the sample compartment, anda sampling flow rate control unit that delivers the sample from thepatient into the sample compartment at a desired rate, wherein thesample compartment volume and the desired rate are determined based onthe defined maximum breathing parameter frequency.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 graphically describes a typical breath waveform based on a carbondioxide measurement taken on gas drawn from a breath.

FIG. 2 graphically describes a typical breath waveform based on anairway pressure measurement taken at the proximal airway.

FIGS. 3A-3C graphically describe how breath CO may vary with the phaseof the breath and one variation of using capnometry or airway pressureto identify the end-tidal period of the breath. FIG. 3A describes the COlevel in the breath for different phases of the breathing cycle. FIG. 3Bdescribes the CO₂ level in the breath for different phases of thebreathing cycle and threshold values to identify the end-tidal period.FIG. 3C describes the proximal airway breathing pressure for differentphases of the breathing cycle and threshold values to identify theend-tidal period.

FIG. 4A describes a capnometry signal for different phases of thebreathing cycle and one variation of a differential of the signal foridentifying different portions of the breath. FIG. 4B describes anairway pressure signal for different phases of the breathing cycle andone variation of a differential of the signal for identifying differentportions of the breath.

FIG. 5A describes schematically an overview of one variation of a breathcapturing system. FIG. 5B describes schematically an overview of anothervariation of a breath capturing system.

FIG. 6 provides a collection of graphs illustrating the phase shiftassociated with using capnometry to identify and collect a breathsample.

FIG. 7 provides a collection of graphs illustrating the phase shiftassociated with using airway pressure monitoring to identify and collecta breath sample.

FIGS. 8-9G describe one variation of a breath analysis device using abreath rate correction factor to correct for breath rate relatedvariations in the heterogeneity of the sampled gas, when using a fixedsampling flow rate with a fixed sampling time and a fixed samplecollection tube volume. FIG. 8 is a graph of a capnometry signal for asequence of breaths. FIG. 9A is a graph of a breath capnometry waveformrepresentative of a nominal breath rate. FIG. 9B is a graph of a breathcapnometry waveform representative of a relatively fast breath rate.FIG. 9C describes the system of FIGS. 5A or 5B capturing an end-tidalgas sample from the breath shown in FIG. 9A. FIG. 9D describes thesystem of FIGS. 5A or 5B capturing an end-tidal gas sample from thebreath shown in FIG. 9B. FIG. 9E shows use of a breath rate correctionfactor to compensate for non-homogeneity of the captured gas sample,using a breath simulator and known CO gas input, with and without acorrection factor applied. FIG. 9F describes an alternate configurationof the system shown in FIG. 9D in which the end-tidal sample is placedin the valve V1 side of the sample tube. FIG. 9G describes the system ofFIGS. 9C and 9D in which a breath is captured from a relatively slowbreath rate.

FIGS. 10A-10B describe one variation of a method of modulated multiplebreath sampling for capturing a targeted volume of end-tidal gas andsubsequent gas analysis. FIG. 10A is a schematic flow diagram describingthe multiple breath sampling technique. FIG. 10B illustrates a graph ofthe number of breaths that may be necessary to fill an exemplary samplevolume for a series of breath rates.

FIGS. 11A-11F describe one variation of a breath-rate-modulated multiplebreath sampling technique for capturing a targeted volume of end-tidalgas and subsequent gas analysis. FIG. 11A graphically describes thecapnometry signal and sample capture valve position, of an exemplarybreath rate modulated multiple breath sampling protocol. FIGS. 11B-11Fdescribe the pneumatic system described in FIGS. 5A or 5B for anexemplary end-tidal gas capture. FIG. 11B describes the pneumatic gascapture system of FIG. 5A or 5B with end-tidal gas from the first breathbeing captured. FIG. 11C describes the pneumatic gas capture system ofFIGS. 5A or 5B with the second breath being staged for capturing. FIG.11D describes the pneumatic gas capture system of FIGS. 5A or 5B withend-tidal gas from the second breath being captured. FIG. 11E describesthe pneumatic gas capture system of FIGS. 5A or 5B with the third breathbeing staged for capturing. FIG. 11F describes the pneumatic gas capturesystems of FIGS. 5A or 5B with end-tidal gas from the third breath beingcaptured.

FIGS. 12A-B describe one variation of a method of modulated variablesampling flow rate for capturing a targeted volume of end-tidal gas andsubsequent gas analysis. FIG. 12A describes a schematic flow diagram ofthe sequence of operation of a breath-rate-modulated variable samplingflow rate technique. FIG. 12B illustrates a graph of a sampling flowrate versus corresponding end-tidal time periods for an example samplevolume.

FIGS. 13A-13F describe one variation of a breath-rate-modulated variablesampling flow rate technique for capturing a targeted volume ofend-tidal gas for subsequent analysis. FIG. 13A graphically describes abreath capnometry signal for a relatively fast breath rate. FIG. 13Bgraphically describes a breath capnometry signal for a relatively slowbreath rate. FIG. 13C describes a pneumatic diagram of the gascollection system for the breath shown in FIG. 13A for an exemplaryend-tidal gas capture, adjusted to a relatively fast sampling flow rate.FIG. 13D describes a pneumatic diagram of the gas collection system forthe breath shown in FIG. 13B, adjusted to a relatively slow samplingflow rate. FIG. 13E describes using a capnometry signal to determine anaverage end-tidal time of previous breaths and a respective adjustmentof the sampling flow rate to collect the targeted volume of end-tidalgas from a single subsequent breath. FIG. 13F describes using an airwaypressure signal to determine a projected end-tidal time from ameasurement of a pre-end-tidal period, and a respective adjustment ofthe sampling flow rate to collect the targeted volume of end-tidal gasfrom the breath.

FIGS. 14A and 14B describe derivation and use of correction factorequations to adjust for the heterogeneity of end-tidal gas. FIG. 14A isa graph illustrating ETCO ppm as a function of breath rate. FIG. 14Bprovides at table with some exemplary breath rate correction factorequations.

FIG. 15A illustrates a method for creating a look-up table to convertmeasured ETCO at a given breath rate to a corrected ETCO. FIG. 15Bprovides a graph of ETCO accuracy. FIGS. 15C provides a graph comparingslope and offset to breath rate. FIGS. 15D provides a graph comparingslope and offset to breath rate. FIG. 15E provides a look-up table andsome exemplary compensation equations.

FIG. 16A illustrates a method of determining a gas sampling rate of aflow generator to correlate to an upper limit breath rate andpredetermined sampling volume. FIG. 16B illustrates the pneumatic gascapture system of FIGS. 5A or 5B drawing a patient's breath at an upperlimit breath rate. FIG. 16C illustrates the pneumatic gas capture systemof FIGS. 5A or 5B drawing a patient's breath at a breath rate below anupper limit breath rate.

DETAILED DESCRIPTION

Described here are devices and methods for capturing and analyzing anexhaled breath. In some variations, one or more breathing parameters aremeasured to identify the different constituent portions of a breath andthe respective time periods, and a pneumatic system is used forcapturing the portion of exhaled breath in a sampling tube using anidentified time period. In some variations, one or more valves and/orflow control mechanisms—such as a vacuum pump, for example—are used toregulate the flow rate of gas drawn into the sampling tube. In somevariations, the captured portion of breath is analyzed for indicationsof a patient's physiological state.

A portion of a breath may include an end-tidal portion, a beginningportion, a middle portion, and an end portion of an exhaled breath.Measured breathing parameters may include one or more of carbon dioxide,oxygen, airway pressure, airway temperature, breath flow rate, andbreath pressure. Identifying the time period of a portion of a breathmay include identifying approximately the start and termination of thattime period.

In some variations of a multiple breath end-tidal sample collectionalgorithm, the number of samples collected varies with the breath rate,in order to fill a fixed sample collection volume with the completeend-tidal portion of the breath(s). In some variations of a variablesampling vacuum rate algorithm, vacuum rate is modulated based on abreath rate, allowing the sample collected to be the entire end-tidalsection of the breath.

The composition of exhaled gas may vary corresponding to differentstages of the expiratory period. For example, gas sampled near the endof exhalation may be representative of gas that has most recentlydiffused out of the blood stream into the alveoli. In the example shownin FIG. 1, described below, the expiratory period is divided into twoportions: pre-end-tidal and end-tidal. During the pre-end-tidal portion,gas from the conducting airways and from the distal portions of the lungare expelled, and during the end-tidal portion, gas that has freshlydiffused into the alveolar volume is expelled. A diagnostic gas samplemay be best taken from the end-tidal period, for example when attemptingto diagnose a physiologic condition in the blood stream, such ashyperbilirubinemia or hemolysis. For explanatory purposes, exemplaryvariations for sampling end-tidal gas for end-tidal CO measurement aregiven below, however the principles apply to other diagnostic purposes.

FIG. 1 graphically describes a typical breathing pattern 100 from theperspective of a carbon dioxide (CO₂) signal measured in breath drawnfrom the person's airway, such as from their nose, as a function oftime, with time on the horizontal axis, and CO₂ level on the verticalaxis. During the expiratory phase CO₂ is expelled, hence the CO₂ levelincreases. During the inspiratory phase, ambient air occupies the nose,hence the measured CO₂ drops to essentially zero. There may be a varietyof shapes to a breath CO₂ curve, based on the person's breathingpattern, their age, how they are breathing and any underlying acute orchronic medical conditions. Some curves may show the followingsub-portions for the expiratory phase: (1) a beginning portion of low orno CO₂ because the gas may simply be gas from the proximal airway devoidof CO₂, (2) a middle portion showing CO₂ rapidly increasing from zero tothe CO₂ level at the distal segments of the lungs, (3) an end-portionshowing a plateauing or leveling off of the CO₂, representing the CO₂coming from the alveoli for that exhaled breath, and (4) potentially aconstant peak level at the very end of the expiratory period. However,there can be many other curves different from this classic curve. PeakCO2 levels may be 4-6% during the end-tidal period and close to or equalto zero during the inspiratory period.

In some variations, the level of CO₂ in an exhaled breath is used todetermine the duration of a period of a breath. In further variations, aduration of a period of breath may be characterized by a start and atermination of that period. In some variations, a CO₂ level is used todetermine a start or a termination of a period of a breath. In othervariations, a first time derivative of a CO₂ level is used to determinea start or a termination of a period of a breath. In yet othervariations, a second time derivative of a CO₂ level is used to determinea start or a termination of a period of a breath. In some variations, acombination of CO₂ levels and CO₂ level time derivatives may be used todetermine a start or a termination of a period of a breath. In somevariations, a start of an end-tidal period may be determined by a changein the first time derivative of a CO₂ level of the exhaled breath, suchas a sudden decrease in the first time derivative of the CO₂ level. Insome variations, a decrease in the first time derivate of the CO₂ levelis more than a 10% decrease. In some variations, a decrease in the firsttime derivate of the CO₂ level is more than a 25% decrease. In somevariations, the derivative will approach or become zero showing verylittle rate of change or a peak plateau, respectively. In othervariations, the start of an end-tidal period may be determined by alarge second time derivative of the CO₂ level. In some variations, atermination of an end-tidal period may be determined by a maximum CO₂level, which may be detected or confirmed by a change in the sign of thefirst time derivative of the CO₂ level as the derivative becomesnegative (associated with a drop of the CO2 level from its peak value).In further variations, a start of a beginning period may be determinedby a sudden increase in the first time derivative of the CO₂ level. Inother variations, the start of a beginning period may be determined byan increase in the CO₂ level from zero CO₂ level. In some variations,the increase in CO₂ level may be non-zero, such as near-zero or from abaseline. In some variations, a termination of a middle period may bedetermined by a change in the first time derivative of a CO₂ level ofthe exhaled breath, such as a sudden decrease in the first timederivative of the CO₂ level. In some variations, a CO₂ level, first timederivative thereof, second time derivative thereof, or a combination ofthe foregoing may be used to determine the start and termination of oneor more periods.

FIG. 2 graphically describes a typical breathing signal 200 from theperspective of measured airway pressure, showing a negative pressureduring inspiratory phase and a positive pressure during expiratoryphase. During at rest breathing, the peak expiratory pressure maycorrespond to the middle of the expiratory phase and the start of theend-tidal period. In FIGS. 1 and 2, TI, TE, TPET, TET, TPE representinspiratory time, expiratory time, pre-end-tidal time, end-tidal time,and post expiratory time respectively. An inspiratory pause may also bepresent (not shown), in which lung muscle movement during inspiration ispaused before the expiratory period begins. Peak inspiratory pressuremay be −1 to −4 cwp during restful breathing, and up to −15 cwp duringheavier breathing, and peak expiratory pressure may be +0.5 to +2.0 cwpduring restful breathing and up to +10 cwp during heavier breathing whenmeasured at the entrance to the nostrils. One of skill in the art willreadily recognize that the cwps given here are exemplary and that othercwps may be present without deviating from the scope of this disclosure.

In some variations, airway pressure is used to determine a start or atermination of a period of a breath. In other variations, a first timederivative of an airway pressure is used to determine a start or atermination of a period of a breath. In yet other variations, a secondtime derivative of an airway pressure is used to determine a start or atermination of a period of a breath. In some variations, a combinationof airway pressures and airway pressure time derivatives may be used todetermine a start or a termination of a period of a breath. In somevariations, a start of an end-tidal period is determined by maximumairway pressure, that is, by a zero first time derivative of the airwaypressure. In some variations, a termination of an end-tidal period maybe determined by zero airway pressure. In some variations, an airwaypressure, first time derivative thereof, second time derivative thereof,or a combination of the foregoing may be used to determine the start andtermination of one or more periods.

In some variations, the breath sensor monitors the person's breathingover time, and trends the breathing pattern by determining a continuallyupdated value that is characteristic of the breathing pattern. Forexample, peak positive values of a breathing signal may be measured andupdated for each breath. Peak values may be compared with previous peakvalues. Peak values may be averaged over a previous number of multiplebreaths. Similarly, time-related aspects of the breaths may be trended,such as the expiratory time. Various breath-related events that are notnormal breaths may be identified and exception algorithms may exist inorder to not include these non-normal breath events inadvertently indeterministic steps. For example, the characteristic waveform of asneeze, cough, stacked breath, or non-full breath may be defined inadvance or based on monitoring of a particular patient, and whendetected by the breathing sensor, excepted from the appropriatedeterministic algorithms.

FIGS. 3A-3C describe in more detail one variation of using a breathsignal to identify a portion of the breath cycle for capturing a desiredsample for compositional analysis. In the example shown, a capnometrysignal or an airway pressure signal is used to identify the end-tidalportion of the expiratory phase for measurement of end-tidal CO. In FIG.3A, the breath CO level 300 is represented, showing how CO varies withthe breath cycle, where the peak CO value corresponds to the end-tidalperiod. The peak CO value 310 is the value of interest, as it is themost closely correlated to the CO level in the blood. In the capnometryexample 330 in FIG. 3B, time and amplitude threshold values areestablished to determine the beginning and end of the end-tidal period.YA and YB are the CO₂ amplitudes at the slope transition point and peaklevel respectively, representing the beginning and ending end-tidal CO₂amplitudes respectively. XA and XB are the durations of thepre-end-tidal period and expiratory period respectively, measured fromt1′, the start of the expiratory period as defined by an increase fromthe baseline CO2 level. Thresholds Y1, Y2, X1 and X2 can be respectivelyestablished from and based on trending, averaging, pattern recognitionor other protocols of YA, YB, XA and XB, for example a percentage of amoving average trended value with exceptions disregarded. In the airwaypressure example 360 of FIG. 3C, YC represents the peak amplitude,corresponding to the start of the end-tidal period, and XA and XBrepresent the duration of the pre-end-tidal period and the expiratoryperiod. Thresholds X1, X2 and Y1 are established from and based ontrending, averaging, pattern recognition or other protocols of XA, XBand YC respectively, and threshold Y2 is established base on the zeropressure. For example, end-tidal gas sample collection can begin, withthe appropriate phase shift, when nasal pressure reaches the peak value,or Y1, or at the midpoint of expiratory phase, XB/2, based on trending,reaches zero, and end when nasal pressure becomes negative, or zero, orwhen it reaches Y2, or after a time delay of XB, or after a time delaybased on previously measured expiratory time. Measuring breathingairflow or proximal airway temperature provides very similar informationto airway pressure, and these signals can also be used in the mannerpreviously described to determine the different portions of thebreathing curve and the end-tidal period. In addition other breathmeasurements can be made to discern the breathing pattern, such assound, ultrasound, vibrations, and plethysmography.

The threshold techniques described in FIGS. 3B and 3C can be highlyreliable when the breath pattern is relatively constant and non-erratic.However, in non-constant or erratic breathing situations, capnometry andairway pressure may not reliably distinguish the beginning and end ofthe end-tidal period. For example capnometry may have difficulty inreliably identifying exactly the transition between the pre-end-tidaland end-tidal periods, because this transition may look different fordifferent breathing patterns. For example, the slope of CO₂ increaseduring the expiratory phase may be constant without the transition pointfrom a first slope to a second slope in FIG. 3B. Or, there may be morethan two CO₂ slopes during the expiratory phase hence more than onetransition, making it potentially arbitrary to determine which slopetransition corresponds to the beginning of the expiratory phase. Theforegoing are merely examples of potential difficulties in identifyingthe beginning of the end-tidal period, and other issues are possible. Aproximal airway pressure signal, with the appropriate algorithms, mayimprove reliability over capnometry in that rarely would there be morethan one peak exhalation pressure for a given breath, making this markera reliable marker. Similarly, the transition from positive pressure tozero pressure, with the appropriate zeroing algorithms, may reliabilitycorrelate to the end of the end-tidal period. Therefore, using proximalairway pressure sensing may provide enhanced fidelity and in additionmay substantially lower cost. Nonetheless, airway pressure may also belimited in its fidelity.

FIGS. 4A and 4B indicate another variation using capnometry and proximalairway pressure to measure the breathing pattern and identify differentportions of the breathing pattern, including the end-tidal period. FIG.4A is a graph 400 of exhaled carbon dioxide and the rate of change(first derivative) of exhaled carbon dioxide. (CO₂ is represented byline 410 and the derivative of CO₂ is represented by line 420.) In FIG.4A the breath CO₂ is measured and the measurement is differentiatedinstantaneously in real time. By observing instant changes in slope andcomparing against the appropriate threshold values (such as thethreshold values described herein), the start of the end-tidal periodcan be reliably identified. And by observing rapid changes from apositive to a negative differentiated value, the end of the end-tidalperiod can be reliably identified. In addition to distinguishing theend-tidal period, other portions of the breath phase can be identifiedusing this technique. In other variations, a second differential of themeasured signal can be utilized to further improve the fidelity orreliability of identifying an exact portion of the breath pattern.

FIG. 4B is another variation using measured proximal airway pressure,differentiated in real time. FIG. 4B is a graph 450 of proximal airwaypressure and the rate of change (first derivative) of the proximalairway pressure. (Airway pressure is represented by line 460 and thederivative of airway pressure is represented by line 470.) A first zerovalue 472 of dPA/dt subsequent to a positive value indicates the peakairway pressure at time t2 corresponding to the start of the end-tidalperiod. A second zero value 474 of dPA/dt subsequent to a negative valueindicates a zero airway pressure value at time t3 corresponding to theend of the expiratory end-tidal period. In addition to manipulating acapnometry or airway pressure signal in this manner, other breathparameters can be likewise manipulated. Examples of such otherparameters include breathing gas temperature, humidity, airflow, soundand others. Although end-tidal CO gas analysis is described in theexamples herein, it should be understood the systems and methods canapply to sampling and analyzing other gases from other portions of thebreathing cycle.

For some breath analysis applications, a minimum quantity of gas volumeis required by the gas composition analyzer in order for it to providean accurate analysis. One technique for obtaining the gas sample foranalysis is to collect the gas in a temporary storage compartment whileit is being drawn from the patient. The storage compartment is sized toa known volume to meet the volume requirement of the gas compositionanalyzer, and for convenience, the compartment can be a fixed orconstant volume. After the compartment is filled with the desired gas,the gas in the compartment can then be sent to the composition analyzerfor analysis. The gas stored and analyzed may be purely from thetargeted portion of exhalation in order to achieve an accurate analysis.Therefore, the system may be capable of obtaining that volume of gasfrom the correct part of the breath, under a wide variety of breathingpatterns, and yet still collect the requisite quantity of gas for theanalyzer to be accurate.

FIG. 5A describes schematically an overview one variation of a devicefor capturing exhaled breath, including a sampling cannula 501 and a gassample collection and analysis instrument 502. Gas may be drawn from thepatient, for example using the sampling cannula 501 and a flow generator512. The flow rate of the flow generator may be measured by a flowtransducer, for example a pressure sensor array, 526 and 528, arrangedsimilarly to pneumotach. The measured flow rate may be used as a closedloop feedback control to control the flow generator flow rate. A breathsensor, such as a capnometer 510 or a pressure sensor 526, may be usedto measure the breathing pattern in real time. Gas from the desiredportion of the breath is captured and isolated in the storage collectioncompartment 518. Gas entering the storage compartment is controlled byat least one valve V1, for example with a common port c always open, anda second open port, either a to collect gas or b to isolate the storagecompartment. There may be a valve V2 between V1 and the flow generatorto participate with V1 in isolating the storage compartment. Gas notbeing captured for analysis is channeled away from the storagecompartment via a bypass conduit 520. The captured gas is sent from thestorage compartment through a gas composition analyzer 514, such as a COsensor. A control system 522 with a microprocessor 524 controls thesystem with the associated algorithms. The flow generator can be avacuum or pressure pump, such as a diaphragm pump, or another type offlow generating device such as a vacuum source, a Venturi from apositive pressure source, or a syringe pump. Valves to manage gasrouting can be an arrangement of 3 way 2 position valves or can be anarrangement of 4 way 3 position valves. Capnometer 510, if used,measures the breathing pattern instantaneously using infrared (IR). Thegas composition analyzer can be an electrochemical sensor with areaction time, or a gas chromatographer, or a mass spectrometer. Othervariations may use different analyzers. The sample storage compartmentcan be a small bore inner diameter tube or conduit of considerablelength in order to minimize the cross section which may reduce gasmolecule interaction along the length of the conduit. The samplingcannula may be a silicone or PVC tube with an inner diameter of0.020-0.080″. Pressure sensor 516 is an additional pressure sensor thatmay be used in tandem with 526 so that a flow rate can be determined, inaddition to using it for airway pressure measurement. Flow rate can beused to adjust the pump speed in some variations that utilize a variableflow rate. Pressure sensor 516 can also be utilized for ambientinformation where the breathing curve is measured by pressure instead ofcapnometry. In some variations, an instantaneous carbon monoxide sensoris used as the breath sensor, in place of a capnometer or an airwaypressure sensor. Other instantaneous breath sensors may also be used.

FIG. 5B describes additional details about the pneumatic operation ofthe system shown in FIG. 5A (see also FIG. 9C below). For similarfeatures in FIG. 5A, a discussion is not repeated here. A bypass tube536 allows the gas being drawn from the patient or from ambient tobypass the sample tube 518 during times which the sample tube may beisolated from these gases. In this arrangement, valve V1 may be closedat port a and valve V2 may be open at port b to allow flow from bthrough c. A flow generator may be used to draw the sampling gas throughthe bypass type. A push tube 532 may be used to push the end-tidalsample in the sample tube 518 out of the sample tube to the sensor 514,at which time valves V1 and V3 are each open at port b and V2 is closedat port a. Valve V4 switches the source gas from patient gas to ambientgas by opening port b, when it is desired to not contaminate theinternal gas pathways with patient gas or for purging the system.

In some variations, the pneumatic system shown in FIGS. 5A and 5B abovemay include a removable sampling compartment (not shown). For example,sample tube 518 may be removable form the system. In this way, thepneumatic system may be able to fill a sample tube with a desired gas,and the sample tube may be analyzed at another location, or preservedfor later analysis. In other variations, the gas may be routed from thesample tube to a removable sampling compartment. In this variation, thecompartment may replace the analyzer or otherwise be positioned so thatit can be removed and/or replaced.

FIG. 6 provides a collection 600 of graphs illustrating the phase shiftassociated with using capnometry to identify and collect a breath samplein one variation of a device for capturing exhaled breath. The top graph610 illustrates actual breath phase (inspiration/expiration). The middlegraph 630 illustrates CO₂ concentration. The bottom graph 660illustrates valve position. The travel time for gas to travel from theperson to the capnometer through the sampling cannula is represented bytα. Therefore the capnometry signal shows a beginning of exhalationslightly after the true beginning of exhalation. The travel time for thegas to exit the capnometer and begin to enter the sample collectioncompartment is represented by tβ. Therefore the sample compartmentisolation valve V1 opens to position at a time t(1), tβ after detectionof the start of the end-tidal period by the capnometer, for the samplecollection time t(s).

FIG. 7 provides a collection 700 of graphs illustrating the phase shiftassociated with using airway pressure monitoring to identify and collecta breath sample in one variation of a device for capturing exhaledbreath. The top graph 710 illustrates actual breath phase(inspiration/expiration). The middle graph 730 illustrates airwaypressure. The bottom graph 750 illustrates valve position. The phaseshift between the actual breath, and the pressure is t4, approximatelyequal to the distance of travel divided by the speed of sound, hence isrelatively instantaneous. The travel time for the gas to exit theperson's airway and begin to enter the sample collection compartment isrepresented by to. Therefore the valve V1 opens to position a at timet(1′), which is tδ after detection of the start of the end-tidal periodby the capnometer, for the sample collection time t(s).

In the following discussion, reference is made to the device forcapturing exhaled breath described above with respect to FIGS. 5A and5B. It should be noted that other devices could be used to determine aduration of a period of an exhaled breath and capture that period ofbreath without deviating from the scope of the disclosure.

In a first variation of a breath-rate-modulated variable, shown in FIGS.8-9G, a correction factor is applied to the gas composition analysisresult to compensate for non-homogeneity of the captured gas sample. Thesystem in the example shown analyzes end-tidal CO gas by identifying theend-tidal period using capnometry, and uses a fixed gas sampling timeand sampling flow rate. FIG. 8 is a graph 800 of a capnometry signal fora series of breaths. The capnometry signal is used to identify a goodbreath to sample and to identify the end-tidal period, with the mostrecent breath on the right end, and the oldest breath on the left end ofthe graph. Breaths 1 through 3 are monitored and assessed for meeting aqualification criteria, and if met, the end-tidal portion of breath 4 issampled for analysis.

FIG. 9A is a graph 900 of a nominal case corresponding to FIG. 8 inwhich breath number 4′s end-tidal period matches the sampling timet(s1). FIG. 9C illustrates the arrangement 930 of a pneumatic system forcapturing the gas described in the nominal case shown in FIG. 9A, inwhich gas from the end-tidal period of Breath 4 completely fills thesample collection compartment volume V(s1),In FIG. 9C, the pre-end tidalof Breath 4 can be seen to the right of V2, out of the samplecompartment. The inspiratory portion of Breath 5 can be seen to the leftof V1, out of the sample compartment.

In the graph 910 of FIG. 9B, the sampling time t(s1) is greater than theend-tidal period. The arrangement 940 shown in FIG. 9D, corresponding tothe graph of FIG. 9B, comprises both end-tidal gas from breath 4 andinspiratory gas from breath 5. For example, if the system is tuned for a1 second end-tidal time with a sample collection time of 1 second, andthe actual end-tidal time is 1 second, then the sample gas ishomogeneous with respect to the different portions of the expiratoryphase, and the analysis may be most accurate (see FIGS. 9A and 9C).However, if the person's end-tidal period becomes shorter or longer induration, the sample compartment may miss some of the end-tidal gas ormay include some non-end-tidal gas, respectively, which may inevitablylead to inaccuracies in the analysis, which can be corrected for byapplication of the gas heterogeneity breath-rate correction factor. Forexample, if the end-tidal time is 0.5 seconds, the sample compartmentmay be 50% filled with pure end-tidal gas from the entire end-tidalperiod plus 50% filled with inspiratory gas, thereby diluting theconcentration of the CO in the sample compartment. Assuming the CO ofthe gas sample from inspiratory phase is known, for example 0.25 ppm,and assuming the analyzer's measurement result is 1.25 ppm CO, and theknown ambient CO is 0.25 ppm, then the sample contains 50% of 0.0 ppmCO, and 50% of 1.0 ppm CO for a corrected CO of 0.5 ppm CO. In this casethe correction factor is 0.5. In the example shown in FIG. 9B, thesampling time t(s1) is greater than the end-tidal period. The capturedgas sample shown in FIG. 9D corresponding to FIG. 9B comprises bothend-tidal gas from breath 4 and inspiratory gas from the next breath.

The resultant CO analysis at 60 bpm shown by the solid line in the graphin FIG. 9E shows a 15% error due to dilution of the sample, howeverapplication of the breath rate dependent correction factor shown by thedotted line achieves 2% accuracy in this example. The correction factormay be a linear equation with a slope and offset value applied to allbreath rates across the operating range of the device.

FIG. 9E describes a graph 950 of accuracy versus breath rate from anend-tidal CO analyzer, using a breath simulator and a known CO gasconcentration input, and a mathematical correction formula. The solidcurve in the graph 950 in FIG. 9E at 40 bpm describes the resultingaccuracy of the CO analysis of the sample collected. In the exampleshown, the sample tube volume and gas sample flow rate are sized and setrespectively to completely fill the sample tube of end-tidal gas fromthe complete end-tidal period, for an end-tidal period of 500milliseconds corresponding to 30 breaths per minute with a 1:1 I:E ratio(“Inspiratory: Expiratory”). As can be seen in the graph, the curve isvery accurate at breath rates below 30 bpm, because at 30 bpm the sampletube is completely filled with homogenous end-tidal gas, and below 30bpm, the sample tube is also filled with homogenous end-tidal gas,although not from the entire end-tidal period. However, above 30 bpm,the sample tube comprises gas from the entire end-tidal period of thebreath sampled, plus some gas from before or after the end-tidal periodbecause the end-tidal periods at these breath rates are shorter induration than the gas sampling time, therefore resulting in a negativeslope in the curve due to the dilution. As can be seen in the correctedcurve, the results at breath rates greater than 30 are accuratelyadjusted with the correction factor. The accuracy between 10 and 30 bpmmay not be linear because at 10 bpm the sample tube contains the veryend of the end-tidal gas, which might be slightly higher in COconcentration than the average throughout the end-tidal period, whereasat 30 bpm, the sample tube contains the gas from the entire end-tidalperiod. The general equation describing the relationship betweenmeasured and actual gas is x=My+B, for example x=0.0074y+0.07, where xis the measured ETCO, M is the slope of the equation, y is breath ratecorrected ETCO, and B is the equation y intercept or offset. ThereforeETCO_((corrected))=└ETCO_((measured))−offset ┘/slope.

FIG. 9F describes an alternate configuration 960 of the system shown inFIG. 9D in which the end-tidal sample is placed in the valve V1 side ofthe sample tube. This is a similar configuration to FIG. 9D, except aportion of the expiratory end-tidal period of breath 4 is captured inthe sample instead of the inspiratory phase (as shown in theconfiguration of FIG. 9D). FIG. 9G illustrates configuration 970 of thesystem of FIGS. 9C and 9D in which a breath is captured from a slowbreath rate. In the configuration of FIG. 9G, some end-tidal gas is notcaptured in the sample tube in the area past V2.

FIG. 10A illustrates a method 1000 for sampling multiple breaths tocollect a targeted volume of end-tidal gas. Method 1000 optionallybegins with step 1002, flushing the system with ambient air. This maynot be necessary every time the method is performed. Method 1000continues with collecting a first end-tidal sample 1004. A valve on asampling tube is opened at the appropriate time to correlate with thebeginning of the end-tidal period. The variation depicted in FIG. 10Aindicates the valve is open to correlate with a second plateau of thefirst derivative of the carbon dioxide concentration, but othervariations may use alternative triggers for the beginning of theend-tidal period, such as those described in this disclosure. The valveon a sampling tube is closed at the appropriate time to correlate withthe end of the end-tidal period. The variation depicted in FIG. 10Aindicates the valve is closed to correlate with a zero of the firstderivative of the carbon dioxide concentration, but other variations mayuse alternative triggers for the end of the end-tidal period, such asthose described in this disclosure. The method with step 1006 todetermine the volume of gas captured in step 1004. The variationdepicted in FIG. 10A indicates the volume based on the pump speed andvalve open time, but other mechanisms could equivalently be used. Thecaptured volume is then compared to the sample tube volume to determineif the sample tube is filled. If not, Step 1008 repeats the capturingstep of 1004 and the comparison of step 1006 until the sample volume isfilled. Then the method, in step 1010, pushes the collected volume to aCO analyzer. In some variations, the collected volume may be pushed to adifferent type of gas analyzer, or pushed to a removable storage tubefor delivery to a lab or other analyzing facility.

As described above, in order to compensate for any breath rate or breathpattern and still obtain the desired sample volume and gas purity,multiple breaths may be sampled. The number of breaths will depend onthe breath pattern and the compartment volume. FIG. 10B illustrates agraph 1020 of the number of breaths that may be necessary to fill asample volume. For exemplary purposes, the sample compartment is 2.5 ml,the sample flow rate is 100 ml/min, and assuming end-tidal gas is beinganalyzed, 3 breaths are needed to be sampled for example at a breathrate of 30 breaths per minute, etc. It should be understood that varyingthe sample compartment, flow rate, etc. may lead to a different graph.Graph 1020 provides an easy reference to determine how many breaths maybe necessary to fill the compartment tube. Although the variation ofFIG. 10B depicts breaths sampled as whole numbers (and, thus, astep-function graph), other variations may use a continuous graph line,thereby indicating that a partial breath (in addition to one or morefull breaths) will be captured to fill the sample volume. Thisinformation may be utilized to close the sample compartment valve at anappropriate time.

FIGS. 11A-11F graphically describe the method of FIGS. 10A-10B using theapparatus of FIG. 5A or 5B, for explanatory purposes. It should be notedthat any number of apparatuses could be used to capture a specificportion of breath without deviating from the scope of the presentdisclosure.

FIG. 11A illustrates a graph 1100 showing the carbon dioxide levels of aseries of breaths. After identifying and assessing the first threebreaths, the system decides to begin collecting samples from the fourthbreath, labeled breath 1. Depending on the prevailing breath pattern,the appropriate number of end-tidal periods are sampled to collect therequisite volume. The breaths may be first verified that they meetnecessary criteria for sampling, resulting in either multipleconsecutive breaths, or non-consecutive breaths. FIG. 11A alsoillustrates a graph 1105 of the valve state of the valve V1 on the inletto the sample tube. While the first three breaths (“breath -3” to“breath -1”) are verified, the inlet to the sample tube is closed (“bopen”). When the system determines to sample breath 1, the inlet to thevalve is opened (“a open”) to allow the sample tube to collect theend-tidal period of breath 1. As can be seen in FIG. 11A, there is aphase shift (time offset) from the beginning of the end-tidal period tothe opening of the inlet valve. This may reflect a finite time requiredfor the breath to travel from the patient to the inlet valve, asdescribed above. When the end-tidal period is over, the inlet valve isagain closed. The open and closing of the inlet valve is then repeatedfor two further breaths.

After storing each sample, before the next sample is stored, the gasbeing drawn from the patient is channeled to bypass the storagecompartment. These configurations of the system is illustrated in FIGS.11B to 11F. In configuration 1110 of FIG. 11B, gas from the firstbreath's end-tidal phase begins to be stored in the sample tube. Inconfiguration 1120 of FIG. 11C, the gas after the first breath'send-tidal phase (i.e., the second breath's inspiratory and pre-end tidalphases) is channeled through the bypass tube. In configuration 1130 ofFIG. 11D, gas from the second breath's end-tidal phase begins to bestored in the compartment. In configuration 1140 of FIG. 11E, the gasafter the second breath's end-tidal phase (i.e., the third breath'sinspiratory and pre-end tidal phases) is channeled through the bypasstube. In configuration 1150 of FIG. 11F, gas from a third breath'send-tidal phase begins to be stored in the compartment, after which thecompartment is completely filled with pure end-tidal gas from multiplebreaths. After this, sample collection can end, and the gas in thestorage compartment can be sent to the gas analyzer for compositionalanalysis. In one variation the sample compartment can be volumetricallysized for a gas sample drawn from a single end-tidal period that isassociated with the longest possible end-tidal duration imaginable. Allother breath rates will result in sampling gas from more than onebreath. In a further variation, in some clinical applications it mightbe desired to size the storage compartment so that the system alwayssamples at least a few breaths or samples breathing for at least 30seconds, in order to collect an average reading over a period of time,to dampen the effect of any breath-to-breath perturbations in the actualgas composition.

FIGS. 12A illustrates a method 1200 of capturing a breath using avariable pump speed to collect a targeted volume of end-tidal gas.Method 1200 optionally begins with step 1202, flushing the system withambient air. This may not be necessary every time the method isperformed. Method 1200 continues with measuring an end-expiratory time1204. In the variation of method 1200, the end-expiratory time could bemeasured using a capnometry signal, differential of capnometry signal,or a pressure signal. In other variations, the end-expiratory time couldbe measured in a different way, such as those described herein. Method1200 then continues with step 1206, adjusting the speed of the pumpbased on the measured end-expiratory time in step 1204. Method 1200 thencontinues to step 1208, where the valve is opened when an end-tidalsample reaches the valve. The valve may remain open for the duration ofthe measured end-tidal time, and then is shut to capture the sample whenthe end-tidal time has passed. Then the method, in step 1210, pushes thecollected volume to a CO analyzer. In some variations, the collectedvolume may be pushed to a different type of gas analyzer, or pushed to aremovable storage tube for delivery to a lab or other analyzingfacility.

As described above, in order to compensate for any breath rate or breathpattern variability and still obtain the desired sample volume, thesample flow rate may be adjusted. FIG. 12B illustrates a graph 1220 of asampling flow rate that corresponds to an end-tidal period. Forexemplary purposes, the sample storage compartment is 1.25 ml and theend-tidal portion of a particular breath is 1 second in duration. Inthat example, the sample flow rate is adjusted to be 1.25 ml/second or75 ml/minute in order to collect a 1.25 ml sample of gas sampled fromthe complete end-tidal period. It should be understood that varying thesample compartment, flow rate, etc. may lead to a different graph.

FIGS. 13A-13F describe the method of FIGS. 12A-12B using the apparatusof FIGS. 5A or 5B, with two breathing cases for comparison. It should benoted that any number of apparatuses could be used to capture a specificportion of breath without deviating from the scope of the presentdisclosure. Graph 1300 in FIG. 13A represents “Case A,” a relativelyfast breath. Graph 1310 in FIG. 13B represents “Case B,” a relativelyslow breath. Case A and B result in relatively short and long end-tidaltimes respectively. In configurations 1320 and 1330 of FIGS. 13C and13D, respectively, the system has a fixed sample compartment volume,V(s1), for example 1.0 ml. It will be understood that other volumes ofsample tubes may be used without deviating from the scope of thedisclosure. In Case A (FIGS. 13A and 13C), the end-tidal duration is 0.4seconds and hence the sampling flow rate is adjusted to 150 ml/min, inorder to draw a 1.0 ml gas sample in 0.4 seconds. In Case B (FIGS. 13Band 13D), the end-tidal duration is 0.833 seconds and hence the samplingflow rate is adjusted to 50 ml/min in order to draw a 1.0 ml gas samplein 0.833 seconds. Therefore, in both Case A and B, the entire end-tidalperiod is sampled for analysis, rather than just a portion of theend-tidal period, and the sample collection compartment contains pureend-tidal gas and is 100% filled with end-tidal gas. The correct amountof gas, 1 ml, may be sent to the gas CO analyzer in both cases for anaccurate analysis. In other embodiments, the gas may be pushed to adifferent type of gas analyzer, or pushed to a removable storage tubefor delivery to a lab or other analyzing facility. The speed of the pumpcan be precisely regulated by modulating the voltage or current drivingthe pump, based on look up tables in associated software. In someembodiments, the speed of the pump may be precisely regulated using aclosed loop feedback control system by measuring the flow rate of thefluid, for example using a pneumotach as described in FIG. 5A and 5B,and adjusting the speed of the pump by adjusting the current based onthe measured flow rate. In some embodiments, a look up table may be usedto apply a current to the pump depending on the desired flow rate, then,in addition, a pneumotach feedback loop may be used to make fineadjustments to the current to precisely obtain the exact flow rateneeded.

FIG. 13E illustrates a graph 1340 which describes the variable samplingflow rate technique of FIG. 12A when capnometry is used to measure thebreathing pattern, showing a series of breaths with the most recentbreath on the right end of the graph. After determination of an averageend-tidal time from a series of preceding breaths (Breaths 1-3), thesample flow rate is adjusted from a baseline default sampling flow rateof Q(d) to sampling flow rate of Q(s), equal to the compartment volumeV(s1) divided by the projected end-tidal time or sampling time t(s).Using the closed loop control of the flow generator, the flow is finetune adjusted until it equals Q(s) (during Breath 4). Then gas from theend-tidal period of a subsequent breath (Breath 5) is drawn at flow rateQ(s) and brought into the sample collection compartment. Additionally,the end-tidal time of the breath that was sampled can be measured toconfirm it was equal to t(s) in order to validate the integrity of thesample. If the breath was erratic not conforming to t(s), then thesample can be discarded and the procedure repeated.

FIG. 13F illustrates a graph 1350 which describes the variable samplingflow rate technique of FIG. 12A when using airway pressure to measurethe breathing pattern, showing a series of breaths with the most recentbreath on the right end of the graph. In the example shown, end-tidalgas from breath 3 is sampled for analysis. The sample flow rate can beadjusted in a variety of ways. In one variation, the end-tidal time canbe predicted from earlier breaths and the flow rate adjusted accordinglyprior to drawing the sample from the targeted breath. In othervariations, an adjustment to the flow rate can be made instantaneouslybased on the pre-end-tidal duration T(e) after T(e) is measured andknown.

In some variations, a measured gas concentration may be adjusted toapproximate an actual gas concentration. Such adjustments may accountfor variations in the fidelity of a breath sampling apparatus over arange of breath rates. The measured concentration may be modified usinga correction equation, which may be specific to the apparatus beingused, but may also be usable across various apparatuses. In somevariations, the correction equation is formulated to cover a range ofbreath rates. In some variations, a breath rate and a measurement of agas concentration in the apparatus may be sufficient to approximate theactual concentration of the gas at an inlet of the apparatus using acorrection equation.

FIG. 14A is a graph 1400 illustrating ETCO ppm as a function of breathrate. In the example shown the actual ETCO ppm is 4.1 ppm. Graph 1400depicts three curves: a measured value, a breath rate corrected value,and an actual value. The actual value may represent a gas concentrationat the inlet to a breath sampling apparatus. The measured value mayrepresent a gas concentration measured at another point in the breathsampling apparatus, such as an outlet. The breath rate corrected valuemay represent the measured value of the gas concentration after it hasbeen adjusted. To generate graph 1400, four measurements of gasconcentration may be taken for four breath rates: 10 bpm, 30 bpm, 40bpm, and 60 bpm. As graph 1400 illustrates, the breath rate correctedvalue approximates or matches the actual value. The breath rate may becorrected using one or more breath rate correction factor equations.

Table 1420 in FIG. 14B provides some exemplary breath rate correctionfactor equations. Each equation relates the measured gas concentration(y) to the breath rate (x). In one variation, the breath rate correctionfactor equation is linear. In further variations, the breath ratecorrection factor comprises multiple linear equations, with eachequation providing a correction for a specific range of breath rates.Using different ranges may improve the fidelity of the correction. Inanother variation, the breath rate correction factor equation is aquadratic equation. In further variations, multiple quadratic equationsmay be used for multiple breath rate ranges.

In some variations, the coefficients of a linear or quadratic equationare determined by using a breath simulator. In such variations, thebreath simulator provides a known concentration of a gas at the inlet toa breath sampling apparatus at a known breath rate. From the breath rateand the deviation of measured gas concentration at another location ofthe sampling apparatus from known gas concentration at the inlet, a ratefactor equation is derived by fitting the measurements to an equation.For example, the embodiment depicted in FIG. 14A may provide a deviationfor each discrete breath rate. The deviation at each breath rate can beextrapolated to produce one or more equations spanning the operatingrange. In this way, a measured gas concentration can be corrected toapproximate an actual gas concentration for any breath rate within theoperating range.

Further variations may provide adjustments for a range of measured gasconcentrations to a range of corrected gas concentrations over a rangeof breath rates. In one variation, a method for deriving a breath ratecorrection equation may include deriving multiple polynomial equationsthat span the ranges of measured gas concentrations, actual gasconcentrations, and breath rates and utilizing the polynomial equationsto populate a look-up table. In other variations, an apparatus mayinclude a processor that references a look-up table to determine apolynomial equation for a given breath rate, where the polynomialequation provides a corrected gas concentration for a measured gasconcentration at the given breath rate. In this way, variations of thepresent disclosure may beneficially provide for determining a gasconcentration in a patient's breath independently of patientcooperation. That is, the gas concentration may be determined forpatients who are unwilling or unable to regulate their breathing tocorrelate to a “normal” breathing pattern.

FIG. 15A illustrates method 1500 for creating a look-up table to convertmeasured ETCO at a given breath rate to a corrected ETCO, in accordancewith one variation. The method may begin by establishing ETCO accuracyfor discrete breath rates and for discrete known gas concentrations(step 1502). In the variation shown in FIG. 15A, the discrete breathrates and gas concentrations are taken to span an operating range, butit should be understood that the discrete breath rates or gasconcentrations need not span the entire range. In some variations, thediscrete breath rates may cover a subset of the operating range and themethod may extrapolate that subset to a broader range, if necessary. Forexample, a look-up table covering an operating range of 8 bpm to 60 bpmmay, in one variation, be populated by taking measurements at 10 bpm, 30bpm, and 50 bpm.

Although ETCO is specifically discussed with respect to FIGS. 15A-E, thedisclosure is not limited to ETCO. In other variations, the methodsdescribed herein may be applied to other gases and/or breath stages andmultiple gas concentrations. Other influencing variables may also beincluded in the database creation, such as different operatingtemperatures, different secondary gas levels, or the like.

In some embodiments, the look-up table may be populated by drawing aknown ETCO through an inlet of an apparatus and then measuring the ETCOat another point in the apparatus. The procedure may be repeated formultiple breath rates.

A specific variation of establishing ETCO accuracy, such as in step1502, is depicted in graph 1520 of FIG. 15B. Graph 1520 illustrates ameasured gas concentration (y axis, “Measured ETCO”) for three known COconcentrations (x axis, “Actual CO”). The measurements are repeatedacross five breath rates: 10 bpm, 20 bpm, 30 bpm, 40 bpm, and 50 bpm;and at three gas concentrations: 0.91 ppm, 9.70 ppm and 24.4 ppm.Although the variation of FIG. 15B shows five specific breath rates andthree gas concentrations, other variations may use a different numberand/or different rates and concentrations.

Returning to FIG. 15A, method 1500 continues with step 1504. At thisstep, accuracy equations for discrete breaths are established. As usedherein, “an accuracy equation” can be understood to be a polynomialequation that fits the measured gas concentrations to actual gasconcentrations of a breath rate, wherein data “fits” an equation whenthe data is interpolated, extrapolated, or smoothed. The equation neednot correlate with the data correctly and may approximate the data. Thedegree of approximation may be determined by the requirements of aspecific application.

In some variations, non-polynomial equations may be used to describe therelationships, such as logarithmic equations, exponential equations, orother equations. Specific accuracy equations are illustrated in graph1520 of FIG. 15B. For each of the breath rates, a linear equation isderived that approximates “Actual CO” to “Measured ETCO” across all“Actual CO” concentrations. The linear equation is derived by fittingthe known CO concentrations and measured ETCO concentrations for eachbreath rate.

Although the variation in FIG. 15B illustrates a linear equation, othervariations may include polynomial equations of higher orders. Forexample second, third, and fourth order polynomial equations. In somevariations, the maximum order may be one less than the number ofmeasurements taken. For example, three measurements were taken in theembodiment illustrated in FIG. 15B and so the maximum order for thepolynomial equation may be two (i.e., a quadratic equation). In FIG.15B, the measurements resulted in a linear equation, but need not have.However, a linear equation may be beneficial because it may require lesscomputing resources to solve. In some variations, the measurements maybe fit to an equation of less than the maximum order. In suchvariations, it may be beneficial to fit the measurements to a “best-fit”equation of a lower order to reduce the need for computing resources.

Referring again to FIG. 15A, method 1500 then moves to step 1506 andestablishes a continuous relationship between the accuracy equations andbreath rate. In this step, the coefficients are collated by the order ineach of the breath rate accuracy equations. For each order, thecoefficients for that order and each coefficient's corresponding breathrate is used to determine the continuous relationship.

FIGS. 15C and 15D illustrate two such comparisons. FIG. 15C illustratesgraph 1530 which plots the slope (M) and offset (b) of the linearaccuracy equations with the discrete breath rates between 10 and 30.Similarly, FIG. 15D illustrates graph 1535 which plots the slope andoffset of the linear accuracy equations with the discrete breath ratesbetween 30 and 50. Two separate ranges may allow for lower orderequations to be derived for the coefficients, thereby reducing theamount of computer resources necessary to solve the equations. Further,by reducing the breath rates to two separate ranges, the fidelity of thesystem may be improved. For example, FIG. 15C and 15D illustrate twoequations which have a constant second derivative. A higher orderpolynomial equation may result in a non-constant second derivative,thereby resulting in possible wide variances in the region of a measuredconcentration.

Although FIG. 15C and 15D depict a separation of the breath rates intotwo ranges, other variations may not separate the breath rates intoranges. Other variations may separate the breath rates into three, four,or five, or more than five ranges.

Returning to FIG. 15A, method 1500 continues with determining equationsfor the slope and offset of the accuracy equations based on thecontinuous relationship established, step 1508. In some embodiments,steps 1506 and 1508 may be performed at the same time, that is,determining the relationships between the continuous relationship mayresult in determining the slope and offset equations. FIG. 15C and 15Dillustrate quadratic equations derived from the relationship between thecoefficients of the accuracy equations and the breath rates. Each of thequadratic equations in FIGS. 15C and 15D has a coefficient at each order(which may include a coefficient=0 in some variations). Thesecoefficients are used in the next step of method 1500.

Although FIGS. 15C and 15D illustrate quadratic equations, polynomialequations of other orders may be used. For example, first order(linear), third order, fourth order, fifth order, sixth order, or higherorder polynomial equations could be used. The maximum order of thepolynomial equations may be the number of discrete breath rates minusone. As in FIGS. 15C and D, the polynomial equations could compriselower orders than the maximum orders. This may improve fidelity if somediscrete regions of the curve can represent a lower order curve. Thismay also reduce the use of computing resources because the difficulty ofsolving a polynomial equation increases as the order increases.

Returning again to FIG. 15A, Step 1510 sets up a look table based on thecoefficient equations determined in the previous step. Referring now tothe exemplary embodiment in FIG. 15E, the look up table can be found onthe bottom of Table 1540. For a given breath rate (less than or equal 30or greater than 30), coefficients for each order of quadratic equationcan be identified. There are two equations derived for each of slope andfor offset. Because slope and offset are determined by quadraticequations in FIGS. 15A-E, the look-up table includes three coefficientsfor each of slope and offset at each breath rate.

FIG. 15E also provides one variation of correcting a measured gasconcentration. Once a breath rate is determined, the relevantcoefficients are determined. Once the relevant coefficients aredetermined, the equations for slope and offset can be determined. Usingthe breath rate, actual values for slope and offset can be determined.These values are then used to calculate the corrected concentrationusing the following formula:

ETCO_((BR Corrected))=[ETCO_((Measured)) −b]/M

It should be understood that the above equation may vary if the numberof coefficients of the accuracy equation is varied. For example, thevariation of FIG. 15E had two coefficients. Thus, the above equationresults from solving a linear equation (two coefficients). If morecoefficients are used, then a solution to a higher order equation may benecessary. The solution may be obtained using any mathematical techniquecapable of solving for an unknown variable in a higher order equation.

When the apparatus is in use, should the measured breath rate ormeasured gas concentration be outside of the ranges defined by the aboveprocedure, the apparatus may react in a variety of ways, depending onthe details of the clinical application. The apparatus may not compute acorrected ETCO result and notify the user that the measured parametersare outside of the apparatus's range. The apparatus may compute thecorrected ETCO despite being out of range, and provide the result to theuser while notifying the user that the accuracy of the result may beless accurate because the measured parameters are outside of theoperating range. In some variations, the apparatus may simply compute aresult by extrapolating with the appropriate equations. In this way,variations of the present disclosure may beneficially provide fordetermining a gas concentration in a patient's breath independently ofpatient cooperation. That is, the gas concentration may be determinedfor patients who are unwilling or unable to regulate their breathing tocorrelate to a “normal” breathing pattern.

In some variations, the entire set of values within an operating rangemay be tested in advance, and a look-up database created based on theresults. For example, breath rates of 10, 11, 12 and so on to 50 bpm(for example), at gas concentrations of 1.0, 1.1, 1.2 and so on to 25.0ppm can be pre-tested. When the device is in use, the corrected gasconcentration can be obtained by finding the appropriate value in thedatabase for the measured breath rate and measured gas concentration. Insome variations, a combined approach is used such as pre-testing allbreath rates but only a set of discrete gas concentrations within ornear the operating range.

While the above embodiment describes the use of breath rate as thebreathing pattern parameter used in the corrections, it is understoodthat rather than breath rate, the same embodiment may be accomplishedwith any breathing pattern related parameter. Examples of otherparameters include expiratory time, end-tidal time, inspiratory time,inspiratory:expiratory ratio, tidal volume, minute volume, airwaypressure amplitude, capnometry signal amplitude, and the duration of thepositive slope of the capnometry signal.

In some variations, a method of determining a gas concentration at theinlet of an apparatus may include determining the patient's breath rateand measuring the concentration of the patient's breath somewhere elsein the apparatus. As used herein, measured a gas in an apparatus can beunderstood to mean measuring anywhere within the apparatus, such as atan outlet or an interior point in the apparatus, such as in a tube orcompartment. With the measured gas concentration, a database can beaccessed to obtain a plurality of coefficients corresponding to thepatient's breath rate. In the example of FIG. 15E, the plurality ofcoefficients are separated by breath rate into two regions: at or below30 bpm, or at or above 30 bpm. Other variations may arrange thecoefficient's differently. Once the coefficients are obtained, themethod may derive a first plurality of polynomial equations (in FIG.15A-E, the first polynomial equations are quadratic). These equationsprovide coefficients for second plurality of equations (in FIG. 15A-E,the second polynomial equations are linear), where the coefficients arethen used to form a compensation equation (in FIG. 15A-E, thecompensation equation is linear). The compensation equation is then usedto adjust the measured gas concentration to determine the gasconcentration at the inlet.

In some variations, an apparatus may include a processor for carryingout the above method of determining a gas concentration at the inlet ofan apparatus. The apparatus may also include a measuring point, a gasanalyzer for determining a gas concentration at the measuring point, aninlet, and a breath speed analyzer. The processor may access a databasestored on a non-transitory computer readable medium, where the databaseincludes a plurality of coefficients for each breath rate in theoperating range.

In some variations, a sampling system may be tuned for an upper limitbreath rate. For a given sample volume (sample volume may be determinedto meet specifications of a particular application), the flow rate of aflow generator, such as a pump, may be configured to fill the entiresample volume with end-tidal gas for the upper limit breath rate. Forbreath rates lower than the upper limit breath rate, the sample volumeis completely filled with end-tidal gas, albeit not all of the end-tidalgas for that breath. In further variations, the system may include anupper limit cut-off that limits sampling to breaths at or below theupper limit. In this way, these variations may beneficially preventnon-end-tidal gas from entering the sample volume. Thus, variations ofthe present disclosure may beneficially provide for determining a gasconcentration in a patient's breath independently of patientcooperation. That is, the gas concentration may be determined forpatients who are unwilling or unable to regulate their breathing tocorrelate to a “normal” breathing pattern.

In some variations, a gas sampling flow rate may be determined to fitthe requirements of a particular application. For example, an upperlimit for normal breathing may be described by a breath frequencyparameter, such as 60 bpm. However, for certain patients (such asneonates, for example), a normal breath rate may exceed 60 bpm. In suchan instance, the upper limit may be higher, such as at 100 bpm.Similarly, the sample volume may be chosen to reflect the needs of aparticular application. In some variations, other frequency parametersmay be chosen, such as inspiratory time, breath period, expiratory time,end-tidal time, capnometer signal rise duration, or another parameterthat describes at least a portion of the patient's breathing. In somevariations, an instantaneous carbon monoxide sensor is used.

FIG. 16A illustrates method 1600 of determining a gas sampling rate of aflow generator to correlate to an upper limit breath rate andpredetermined sampling volume. Method 1600 begins with step 1602:defining an upper limit for the breath rate (BR). As discussed above,the upper limit may be determined to meet the requirements of a specificapplication.

Method 1600 continues with step 1604, defining a desired sample volume(V(s)). In the variation of method 1600, the sample volume is sized foradequate and reliable analysis. In other variations, the sample volumemay be sized to factor in other considerations.

Method 1600 continues with step 1606, determining the gas sampling flowrate (Q(S)). In the variation of method 1600, the flow generator is apump, but other flow generators could be used, such as the examplesdescribed herein. The gas sampling flow rate may be calculated to fillthe desired sample volume at the upper limit breath rate.

In some variations, the sampling flow rate is calculated from thefollowing equation Q(S)=T_(E) /V(S), wherein T_(ET) is the estimatedend-tidal period and is a function of the breath rate. In somevariations, T_(ET) may be assumed to be half of the expiratory time,which itself may be assumed to be half of the breath period (inspiratoryand expiratory periods). The breath period (seconds) is 60/breath rate.For example, if the upper limit breath rate is 60 bpm, then T_(ET) maybe assumed to be 0.25 seconds. If the sample volume in this example is0.5 ml, then the sampling flow rate is 2 ml per second.

FIG. 16B illustrates the pneumatic gas capture system of FIGS. 5A or 5Bin configuration 1620. Configuration 1620 includes the gas sampling rateof the pump configured for an upper limit breath rate, and where thepatient's breath rate is at the upper limit. As can be seen in FIG. 16B,the sample volume is entirely filled with end-tidal gas and there is noen-tidal gas outside of the sample volume.

FIG. 16C illustrates the pneumatic gas capture system of FIGS. 5A or 5Bin configuration 1640. Configuration 1640 includes the gas sampling rateof the pump configured for an upper limit breath rate, and where thepatients' breath rate is below the upper limit. As can be seen in FIG.16C, the sample volume is entirely filled with end-tidal gas, but thereis end-tidal gas from the breath outside of the sample volume. FIG. 16Cillustrates the end-tidal gas outside of the sample volume as locateddownstream (to the right) of V2. However, in other embodiments, theend-tidal gas outside of the sample volume may be located upstream (tothe left) of V1, or a combination of upstream of V1 or downstream of V2.In this way, variations of the present disclosure may beneficiallyprovide for determining a gas concentration in a patient's breathindependently of patient cooperation. That is, the gas concentration maybe determined for patients who are unwilling or unable to regulate theirbreathing to correlate to a “normal” breathing pattern.

Some variations include elements and functionality from individualvariations described above, that is, some variations may combinedifferent elements of the different variations described above. Forexample, a user interface of the apparatus may allow the user to enter acertain patient parameter, such as a patient type, for example adult orinfant, or for example premature neonate or full term infant. Thecontrol system of the apparatus will select a preferred breath ratecompensation methodology, selected from the embodiments described above,and use that methodology accordingly. In some variations, the apparatusmay, for example, use the embodiment described in FIG. 16 in which thesystem is tuned for a breath rate of 60 bpm, therefore collecting anundiluted end-tidal sample for any breath rate at or below 60 bpm andtherefore not requiring breath rate compensation. The variation mayfurther allow for collection of breath rates above 60 bpm, where abreath rate compensation algorithm is invoked. The breath ratecompensation algorithm could for example be the collection of end-tidalgas from two breaths in order to fill the sample tube such as describedin relation to FIGS. 10A-11F, or can be the use of a polynomial equationcorrection factor such as described in relation to FIGS. 15A-15E.

In the foregoing descriptions of variations of the invention, theexamples provided are illustrative of the principles of the invention,and that various modifications, alterations, and combinations can bemade by those skilled in the art without departing from the scope andspirit of the invention. Any of the variations of the various breathmeasurement and sampling devices disclosed herein can include featuresdescribed by any other breath measurement and sampling devices orcombination of breath measurement and sampling devices herein.Accordingly, it is not intended that the invention be limited, except asby the appended claims. For all of the variations described above, thesteps of the methods need not be performed sequentially.

1-40 (canceled)
 41. A system comprising: a breath rate sensor formeasuring a breath rate of a patient; a processor operable to execute analgorithm that accepts a breath sample for collection if the breath rateof the patient is at or below a predetermined maximum breath rate, ordiscards the breath sample if the breath rate of the patient exceeds thepredetermined maximum breath rate; a sample compartment that collects anend-tidal portion of the breath sample, the sample compartment having apredetermined volume based on the predetermined maximum breath rate; anda flow generator having a flow rate that fills the predetermined volumebased on the predetermined maximum breath rate.
 42. The system of claim41, further comprising a gas analyzer that measures a concentration of agas within the sample compartment.
 43. The system of claim 42, whereinthe sample compartment contains only the end-tidal portion of the breathsample.
 44. The system of claim 41, wherein the gas is carbon monoxide,carbon dioxide, or oxygen.
 45. The system of claim 41, wherein thepredetermined maximum breath rate is 60 breaths per minute.
 46. Thesystem of claim 41, wherein the predetermined maximum breath rate is 100breaths per minute.
 47. The system of claim 41, further comprising auser interface configured to allow a user to input a patient parameter.48. The system of claim 47, wherein the patient parameter is a patienttype.
 49. The system of claim 48, wherein the patient type is an adult.50. The system of claim 48, wherein the patient type is a prematureneonate.
 51. The system of claim 48, wherein the patient type is a fullterm infant.
 52. The system of claim 47, wherein the patient parameteris the predetermined maximum breath rate.
 53. The system of claim 41,wherein the flow generator comprises a pump.